Findings may help counter vaccine hesitancy

There was no difference in developmental outcomes among children who had a first febrile seizure (FS) shortly after vaccination (vaccine-proximate, VPFS), those who had a first febrile seizure at a more distant time from vaccination (Non-VPFS), and community-recruited children with no febrile seizure (controls), a prospective study found.

“VPFS was not associated with an increased risk of developmental or behavioral problems in young children compared to children with NVPFS or controls,” reported Lucy Deng, MBBS, of University of Sydney in Australia, and coauthors, in Neurology. “Parents and providers should be reassured by the absence of adverse effects of VPFS on the development of children.”

VPFS were defined as occurring from day 0 to 2 after an inactivated vaccine, day 5 to 14 after a live-attenuated vaccine, or day 0 to 14 after a combination of inactivated and live-attenuated vaccines. NVPFS for corresponding vaccine regimens occurred outside those time windows.

The researchers reported results of one-way ANOVA analysis and defined η2 effect sizes of 0.01 as small, 0.06 as medium, and 0.14 as large, where η2 is a measure of the proportion of variance in the three groups accounted for in a given domain.

No significant difference was found between the three groups in any of five domains of the Bayley Scales for Infant and Toddler Development, Third Edition (Bayley III):

  • Cognition, the primary outcome (F 2.645, η2 = 0.024, P= 0.07).
  • Language (F 2.002, η2 = 0.003, P= 0.76).
  • Motor function (F 1.054, η2 = 0.028, P= 0.05; nonsignificant in adjusted analysis).

Two additional Bayley III scales (social-emotional and general adaptive behavior) were also similar in the three groups, as were pre-academic skills assessed with multidomain test batteries, and behavior and executive functioning data obtained from parents.

“This article adds to the substantial and growing literature that vaccines do not cause poor neurodevelopment and can be used by pediatricians, child neurologists, and epileptologists to allay parental fears,” wrote Charuta Joshi, MBBS, of University of Colorado in Aurora, and Liu Lin Thio, MD, PhD, of Washington University in St. Louis, in an accompanying editorial.

“Parents rate their child’s doctor as their most trusted source of vaccine safety information,” they added. “Unfortunately, health care providers often lack the knowledge necessary to address vaccine hesitancy. This study is one that health care providers should remember when discussing vaccine safety with parents.”

Some vaccination hesitancy results from fear of post-vaccination febrile seizures or poor neurodevelopmental outcomes. Although some vaccines like measles-mumps-rubella (MMR) have been associated with febrile seizures, “there is ample evidence that vaccines do not cause autism, epilepsy, or epileptic encephalopathies,” the editorialists noted.

For acute outcomes of seizure and hospitalization, the authors of the present study have previously shown no difference between VPFS and NVPFS groups.

To look at longer term (1-2 year) outcomes, Deng and colleagues identified children ≤30 months of age with first febrile seizure between May 2013 and April 2016 (n=62 VPFS; n=70 NVPFS) and similarly aged community-recruited controls (n=90) who had no febrile seizure in four Australian tertiary pediatric hospitals. This left the study short of a planned 100 participants in each group.

Vaccine exposure was confirmed with immunization records obtained from the Australian Immunization Register. The primary outcome was the cognitive function scale of the Bayley III. This and other data were assessed once at 1 to 2 years after febrile seizure, or age 12 to 42 months in controls.

Nonsignificant differences between VPFS, NVPFS, and controls were seen for male sex proportion, gestational age <28 weeks, birth weight < 1,500 g, and both 1- and 5-minute Apgar scores of 3 or less. In the VPFS group, 85% of febrile seizures occurred after measles-containing vaccines.

Compared with patients with NVPFS, those with VPFS:

  • Were younger at both the time of first febrile seizure (age 3.7 versus 5.1 months, respectively, P=0.04) and at follow-up (4.9 versus 5.1 months, respectively, P=0.001)
  • Had a higher rate of both febrile seizure duration > 15 minutes (24.2% versus 10.0%) and recurrence of febrile seizure in the first 24 hours after the first febrile seizure (24.2% versus 8.6%).

Longer-term febrile seizure recurrence reported at the time of follow-up did not differ between the VPFS and NVPFS groups.

“We found no significant difference between children who had experienced a VPFS and children with NVPFS or no history of seizures on the primary outcome, the Bayley-III cognitive scale,” Deng and coauthors wrote. “In addition, there was no significant difference between groups for the Bayley-III scales of motor, language, social-emotional, or general adaptive functioning.”

“A higher proportion of children with NVPFS had borderline or significant cognitive, motor, or language impairment compared to the VPFS and control groups, but the difference was not statistically significant,” the editorialists noted. “However, this finding may explain how a parent might confuse association with causation even when a febrile seizure occurs too long after a vaccination to be attributed to it.”

Limitations include recruitment that was less than planned and a single developmental assessment. The primary outcome (Bayley III) also has been criticized for overestimating developmental level.

  1. There was no difference in developmental outcomes among children who had a first febrile seizure shortly after vaccination, those who a first febrile seizure at a more distant time from vaccination, and control children with no febrile seizure, a prospective study found.

  2. This study is one health care providers should remember when discussing vaccine safety with parents, the editorialists noted.

Paul Smyth, MD, Contributing Writer, BreakingMED™

This study was funded by Australian National Health and Medical Research Council.

The researchers had no disclosures. The editorialists had no disclosures.

Cat ID: 125

Topic ID: 79,125,730,125,190,31,34,139,44,192